Lisa Stefanacci

Impaired Recognition Memory in Monkeys after Damage Limited to the Hippocampal Region

Monkeys with lesions limited to the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) were impaired on two tasks of recognition memory: delayed nonmatching to sample and the visual paired-comparison task. Recognition memory was impaired in five different groups of monkeys, whether the lesions were made by an ischemic procedure, by radio frequency, or by ibotenic acid. The finding that the hippocampal region is essential for normal recognition memory performance is considered in the context of current ideas about the role of the hippocampus in declarative memory.

INTRINSIC CONNECTIONS OF THE RAT AMYGDALOID COMPLEX : PROJECTIONS ORIGINATING IN THE ACCESSORY BASAL NUCLEUS

The amygdaloid complex plays an important role in the detection of emotional stimuli, the generation of emotional responses, the formation of emotional memories, and perhaps other complex associational processes. These functions depend upon the flow of information through intricate and poorly understood circuitries within the amygdala. As part of an ongoing project aimed at further elucidating these circuits, we examined the intra‐amygdaloid connections of the acessory basal nucleus in the rat. In addition, we examined connections of the anterior cortical nucleus and amygdalahippocampal area to determine whether portions of these nuclei should be included in the accessory basal nucleus (as some earlier studies suggest). Phaseolus vulgaris leucoagglutinin was injected into different rostrocaudal levels of the accessory basal nucleus (n = 12) or into the anterior cortical nucleus (n = 3) or amygdalahippocampal area (n = 2). The major intra‐amygdaloid projections from the accessory basal nucleus were directed to the medial and capsular divisions of the central nucleus, the medial division of the amygdalohippocampal area, the medial division of the lateral nucleus, the central division of the medial nucleus, and the posterior cortical nucleus. The projections originating in the anterior cortical nucleus and the lateral division of the amygdalohippocampal area differed from those originating in the accessory basal nucleus, which suggests that these areas are not part of the deep amygdaloid nuclei have different intra‐amygdaloid connections. The pattern of these various connections suggests that information entering the amygdala from different sources can be integrated only in certain amygdaloid regions.

Some observations on cortical inputs to the macaque monkey amygdala: An anterograde tracing study

We have previously described the origins of neocortical inputs to the lateral nucleus of the macaque monkey amygdala based on retrograde tracing studies. Here we report results from studies that have attempted to confirm the projections from several candidate afferent regions using 3H‐amino acid autoradiography as an anterograde tracer. We have charted, based on the results of 33 separate injections, the topographic distribution of cortical projections throughout the amygdala. Areas TE and TEO of the inferotemporal cortex, portions of the superior temporal gyrus, and the granular region of the insula project primarily to the lateral nucleus, with little or no innervation of other amygdaloid nuclei. In contrast, orbitofrontal, medial prefrontal, and anterior cingulate regions project primarily to the basal and accessory basal nuclei and provide little innervation to the lateral nucleus. The orbitofrontal and medial prefrontal cortices, but not the anterior cingulate cortex, project to medially situated amygdaloid areas such as the cortical and medial nuclei and to the periamygdaloid cortex. The agranular and dysgranular insula, the parainsula, and rostral portions of the superior temporal gyrus project both to the lateral, basal, and accessory basal nuclei and to the medially situated nuclei. Projections to the central nucleus are particularly prominent from these regions. These data are discussed in relation to the hierarchical processing of sensory information that occurs within the amygdaloid complex. J. Comp. Neurol. 451:301–323, 2002.

Organization of connections between the amygdaloid complex and the perirhinal and parahippocampal cortices in macaque monkeys.

Neuroanatomical studies in macaque monkeys have demonstrated that the perirhinal and parahippocampal (PRPH) cortices are strongly interconnected with the hippocampal formation. Recent behavioral evidence indicates that these cortical regions are importantly involved in normal recognition memory function. The PRPH cortices are also interconnected with the amygdaloid complex, although comparatively little is known about the precise topography of these connections. We investigated the topographic organization of reciprocal connections between the amygdala and the PRPH cortices by placing anterograde and retrograde tracers throughout these three regions. We found that there was an organized arrangement of connections between the amygdala and the PRPH cortices and that the deep (lateral, basal, and accessory basal) nuclei of the amygdaloid complex were the source of most connections between the amygdala and the PRPH cortices. The temporal polar regions of the perirhinal cortex had the strongest and most widespread interconnections with the amygdala. Connections from more caudal levels of the perirhinal cortex had a more discrete pattern of termination. Perirhinal inputs to the amygdala terminated primarily in the lateral nucleus, the magnocellular and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. Return projections originated predominately in the lateral nucleus, the intermediate and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. The interconnections between the amygdala and the parahippocampal cortex were substantially less robust than those with the perirhinal cortex and mainly involved the basal nucleus. Area TF was more strongly interconnected with the amygdala than was area TH. Input from the parahippocampal cortex terminated predominantly in the lateral half of the parvicellular division of the basal nucleus but also to a lesser extent in the magnocellular division of the basal nucleus and the lateral nucleus. Return projections originated predominantly in the magnocellular division of the basal nucleus and were directed almost exclusively to area TF.

Topographic organization of cortical inputs to the lateral nucleus of the macaque monkey amygdala: A retrograde tracing study

The objective of this study was to identify cortical areas that project to the lateral nucleus of the macaque monkey amygdaloid complex. Discrete injections of the fluorescent retrograde tracers Fast blue and Diamidino yellow were placed into different locations within the lateral nucleus. Retrogradely labeled cells were mapped using a computer‐aided digitizing system. In the frontal cortex, low numbers of retrogradely labeled cells were observed in medial and orbitofrontal regions (areas 10, 11, 12, 13, 13a, and 14). In the anterior cingulate cortex, low to moderate numbers of retrogradely labeled cells were located in areas 25, 24, and 32. In the insula, there were moderate to high numbers of retrogradely labeled cells in agranular and dysgranular regions. The parainsula cortex also demonstrated a moderate to high number of retrogradely labeled cells. In the temporal lobe, retrogradely labeled cells were most numerous in the rostral (polar) portion of the perirhinal cortex. Large numbers of labeled cells were also located throughout more caudal portions of the perirhinal regions as well as in the entorhinal cortex, area TE, and the superior temporal gyrus. Fewer retrogradely labeled cells were observed in the cortex along the dorsal bank of the superior temporal sulcus, in the parahippocampal cortex, and in area TEO. Although retrograde tracers can provide only limited evidence for topography, we nonetheless noted that the density of retrogradely labeled cells in a cortical area reliably depended on the location of the tracer injection in the lateral nucleus. J. Comp. Neurol. 421:52–79, 2000.

fMRI of Monkey Visual Cortex

While functional magnetic resonance imaging (fMRI) is now used widely for demonstrating neural activity-related signals associated with perceptual, motor, and cognitive processes in humans, to date this technique has not been developed for use with nonhuman primates. fMRI in monkeys offers a potentially valuable experimental approach for investigating brain function, which will complement and aid existing techniques such as electrophysiology and the behavioral analysis of the effects of brain lesions. There are, however, a number of significant technical challenges involved in using fMRI with monkeys. Here, we describe the procedures by which we have overcome these challenges to carry out successful fMRI experiments in an alert monkey, and we present the first evidence of activity-related fMRI signals from monkey cerebral cortex.

A reexamination of the concurrent discrimination learning task: the importance of anterior inferotemporal cortex, area TE.

For 30 years, the concurrent discrimination learning task has figured prominently in studies used to determine the effects of medial temporal lobe damage in monkeys. However, the findings from these studies have been contradictory. We explored the contribution to concurrent discrimination performance of inadvertent damage to area TE by reexamining the behavioral data and histological material from monkeys with medial temporal lobe lesions previously tested in our laboratory. The amount of inadvertent damage to area TE was more predictive of impaired performance on the concurrent discrimination learning task than was the amount of damage to any medial temporal lobe structure, including the perirhinal cortex. These findings resolve earlier inconsistent findings regarding the concurrent discrimination learning task by demonstrating that performance on this task depends on area TE and not on perirhinal cortex or other medial temporal lobe structures.

A human neurodevelopmental model for Williams syndrome

Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1, 2, 3, 4, 5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

When Amnesic Patients Perform Well on Recognition Memory Tests

Extended exposure to study material can markedly improve subsequent recognition memory performance in amnesic patients, even the densely amnesic patient H.M. To understand this phenomenon, the severely amnesic patient E.P., 3 other amnesic patients, and controls studied pictorial material and then were given either a yes-no (Experiment 1) or a 2-alternative, forced-choice (Experiment 2) recognition test. The amnesic patients and controls benefited substantially from extended exposure, but patient E.P. consistently performed at chance. Furthermore, confidence ratings corresponded to recognition accuracy. The results do not support the idea that the benefit of extended study time is due to some kind of familiarity process made available through nondeclarative memory. It is likely that amnesic patients benefit from extended study time to the extent that they have residual capacity for declarative memory.

Detection and explanation of sentence ambiguity are unaffected by hippocampal lesions but are impaired by larger temporal lobe lesions

We address the recent suggestion that the “hippocampal system” is important for understanding ambiguities in language (MacKay et al., J Cogn Neurosci 1998;10:377–394). Seven amnesic patients and 11 controls first decided whether a sentence was ambiguous and then tried to explain the ambiguity. Three amnesic patients with damage limited to the hippocampal formation and one amnesic patient with primarily diencephalic damage performed like the controls in all respects. Thus, the ability to comprehend ambiguity is independent of the hippocampal formation. By contrast, three patients with larger temporal lobe lesions, which extended beyond the medial temporal lobe, were impaired to about the same degree as the noted amnesic patient H.M. (as reported by Lackner, Neuropsychologia 1974;12:199–207; MacKay et al., J Cogn Neurosci 1998;10:377–394). Patient H.M., like our 3 impaired patients, has some damage outside the medial temporal lobe. However, patient H.M. also had additional difficulties on these and other language tests that the patients with larger temporal lobe lesions did not exhibit. Accordingly, it is possible that H.M.s impairment has a different basis. Hippocampus 2000;10:759–770. Published 2000 Wiley‐Liss, Inc.